rs7336489

Positions:

• chr13-59699164-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042517.2(DIAPH3):​c.3320-32318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,134 control chromosomes in the GnomAD database, including 2,165 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2165 hom., cov: 32)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

Genes affected

DIAPH3 (HGNC:15480): (diaphanous related formin 3) This gene encodes a member of the diaphanous subfamily of the formin family. Members of this family are involved in actin remodeling and regulate cell movement and adhesion. Mutations in this gene are associated with autosomal dominant auditory neuropathy 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

DIAPH3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.3320-32318G>A		intron_variant		ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.3320-32318G>A		intron_variant		1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.3110-32318G>A		intron_variant		1		ENSP00000383173.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24630 AN: 152016 Hom.: 2162 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24638 AN: 152134 Hom.: 2165 Cov.: 32 AF XY: 0.165 AC XY: 12259 AN XY: 74382

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.187

Alfa AF: 0.171 Hom.: 2498

Bravo AF: 0.150

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0020
DANN	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7336489; hg19: chr13-60273298;